AAV-mediated Inner ear gene delivery triggers mild host immune responses in the mammalian inner ear

Hearing loss is a common disability affecting the world’s population. However, its treatment options are limited. More recently, adeno-associated virus (AAV)-mediated inner ear gene therapy has shown great promise as a treatment for hereditary hearing loss. However, the host immune responses to AAV-mediated gene therapy in the mammalian inner ear are not well understood. In this study, two serotypes of AAV vectors were injected individually into the mouse inner ear to evaluate the host innate and adaptive immune responses up to one month after inner ear gene delivery. Our results suggest that the host innate and adaptive immune responses to AAV-mediated inner ear gene delivery are limited and mild, which is favorable for its clinical translation.

听力损失是影响全球人群的常见残疾性疾病。然而，目前其治疗选择十分有限。近年来，腺相关病毒（adeno-associated virus, AAV）介导的内耳基因疗法在遗传性听力损失的治疗中展现出巨大应用前景。然而，目前对于哺乳动物内耳中宿主针对AAV介导基因疗法的免疫应答机制尚不明晰。本研究将两种血清型的AAV载体分别注射至小鼠内耳，以评估内耳基因递送后长达1个月内宿主的固有免疫与适应性免疫应答情况。本研究结果显示，宿主针对AAV介导的内耳基因递送的固有与适应性免疫应答程度有限且较为轻微，这对该疗法的临床转化十分有利。